The cell walls of fungi evoke a powerful immuno-stimulatory response, and have been proposed for use as potential anti-infective and anti-tumor drugs. Fungal cells can also activate dendritic cells and prime class II-restricted antigen-specific T cell responses. The majority of the cell wall (50-60%) of pathogenic (Candida albicans) and non-pathogenic fungi (Saccharomyces cerevisiae) is composed of an inner layer of β-glucan (β-1,3- and β-1,6-glucan) covalently linked to a variety of cell surface mannoproteins [Klis, F. M. et al. et al. Med Mycol 39 Suppl 1, 1-8, 2001; Klis, F. M. et al. et al., FEMS Microbiol Rev 26, 239-56, 2002].
Recognition of β-glucans by macrophages is carried out mainly through Dectin-1 with the cooperation of TLRs, including TLR2 [Brown, G. D. et al. et al. Nature 413, 36-7, 2001]. Dectin-1 activity is inhibited by β-1,3-glucans and β-1,6-glucans, with the β-1,3-glucan laminarins having the highest effect. However, oligosaccharide microarray results show that Dectin-1 binds specifically to β-1,3-glucans. Neutrophils are professional killers, whose role in phagocytosis and killing of bacteria and fungi is well characterized. Neutropenic individuals are much more susceptible to bacterial and fungal infections, with return to normal counts playing an important role in resolution of infection. Neutrophils, unlike macrophages, require serum for optimal phagocytosis and killing. The main opsonic receptors are the complement receptor CR3 and the immunoglobulin-binding receptor FcγR. CR3 has a lectin domain [Brown, G. D. et al. Immunity 19, 311-5, 2003] that mediates increased neutrophil motility towards a mixture of β-1,3-glucan and β-1,6-glucan (PGG-glucan) [Wakshull, E. et al. Immunopharmacology 41, 89-107, 1999]. Although neutrophils express Dectin-1 [Taylor, P. R. et al. J Immunol 169, 3876-82, 2002], its role in fungal recognition is not yet clear.